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2009 Grants - D'Adamio

BRI2 and Alzheimer Therapy

Luciano D'Adamio, M.D.
Albert Einstein College of Medicine of Yeshiva University
New York, New York

2009 New Investigator Research Grant

BRI2 is a protein found in nerve cells that, when mutated, is associated with two forms of inherited dementia closely related to Alzheimer's disease. The functions of BRI2 are still being studied, but normal BRI2 binds to amyloid precursor protein (APP), a protein at the focus of Alzheimer research. Furthermore, BRI2 inhibits the ability of APP to be cut into fragments, thereby reducing the production of beta-amyloid, a fragment of APP that forms the amyloid plaques that are characteristic of Alzheimer pathology.

Luciano D'Adamio, M.D. and colleagues are studying custom-designed protein fragments that mimic BRI2. Such BRI2 fragments may be able to bind APP in a manner similar to the full BRI2 protein, and inhibit the cutting of APP into beta-amyloid. Thus, the use of BRI2 fragments is a potential strategy for therapy of Alzheimer's disease and related dementias.

Dr. D'Adamio's team plans to study a variety of BIR2 fragments to identify ones that inhibit the production of beta-amyloid without affecting other important cellular functions. They also hope to find a BIR2 fragment that prevents beta-amyloid from aggregating into clusters or plaques, which are toxic to nerve cells. These studies could lead to the development of drug treatments to slow or halt the development of Alzheimer's disease.